Respiratory disease affecting feedlot cattle causes tremendous losses yearly to the cattle industry. Calves are the most severely affected, and a large number of these calves die. This disease is associated with pathogenic microorganisms, particularly Pasteurellae species, and various stresses, such as transportation and overcrowding.
Shipping fever is the most economically important respiratory disease associated with Pasteurella species. The disease is characterized by sudden onset, usually within two weeks of stress. The symptoms include dyspnea, cough, ocular and nasal discharge, inappetance and rapid weight loss, fever, increased lung sounds, immunosuppression, general depression, viral and/or bacterial infection of the lungs. Various bacteria and viruses have been isolated from affected animals including Pasteurella spp., bovine herpes virus 1, parainfluenza-3 virus, bovine respiratory syncytial virus and Mycoplasma species. The disease typically affects 15-30% of exposed animals and the resulting deaths are typically 2-5% of the exposed population.
Exposure of the animal to stress, plus infection with a variety of viruses, as described above, appears to make the animal susceptible to fibrinous pneumonia caused by P. haemolytica, and to a lesser extent, Pasteurella multocida. For a general background on shipping fever see Yates, W. D. G. (1982) Can. J. Comp. Med. 46:225-263.
P. haemolytica also causes enzootic pneumonia and can infect a wide range of animals, in addition to cattle, including economically important species such as sheep, swine, horses and fowl. P. haemolytica is also frequently found in the upper respiratory tract of healthy animals. Pneumonia develops when the bacteria infects the lungs of these animals. Protection against Pasteurella-associated diseases is therefore economically important to the agricultural industry.
There are two known biotypes of P. haemolytica designated A and T. There are also 12 recognized serotypes which have been isolated from ruminants. Biotype A, serotype 1 (referred to hereinafter as "A1") predominates in bovine pneumonia in North America. Shewen, P. E. and Wilkie, B. N. (1983) Am. J. Vet. Res. 44:715-719. However, antigens isolated from different serotypes appear to be somewhat cross-reactive. See, e.g., Donanchie et al. (1984) J. Gen. Micro. 130:1209-1216.
Previous Pasteurellosis vaccines have utilized whole cell preparations of either live or heat killed bacteria of various serotypes as described in U.S. Pat. Nos. 4,328,210, 4,171,354, 3,328,252, 4,167,560 and 4,346,074. Traditional vaccine preparations, however, have not been effective in protecting against Pasteurella infections. Indeed, vaccinated animals are frequently more susceptible to the disease than their non-vaccinated counterparts. Martin et al. (1980) Can. J. Comp. Med. 44:1-10. The lack of protection offered by traditional vaccines is probably due to the absence of important antigens, virulence determinants, or the presence of immunosuppressive components in the preparations.
Other vaccine preparations have included crude supernatant extracts from P. haemolytica. See, e.g., Shewen, P. E. and Wilkie, B. N. (1988) in Can. J. Vet. Res. 52:30-36. These culture supernatants, however, contain various soluble surface antigens of the bacterium and produce variable results when administered to animals. Other preparations include capsular extracts obtained via sodium salicylate extraction (See, e.g., Donanchie et al. (1984) 130:1209-1216; U.S. Pat. No. 4,346,074), saline extracted antigens (See, e.g., Lessley et al. (1985) Veterinary Immunology and Immunopathology 10:279-296; Himmel et al. (1982) Am. J. Vet. Res. 43:764-767), and modified live Pasteurella mutants.
Still other attempts at immunization have included the use of a purified cytotoxin from P. haemolytica. See, e.g. Gentry et al. (1985) Vet. Immunology and Immunopathology 9:239-250. This cytotoxin, which is a leukotoxin, is secreted by actively growing bacteria. Shewen, P. E., and Wilkie, B. N. (1987) Infect. Immun. 55:3233-3236. The gene encoding this leukotoxin has been cloned and expressed in bacterial cells. Lo et al. (1985) Infect. Immun. 50:667-671. Calves which survive P. haemolytica infections possess toxin-neutralizing anti-body. Cho, H. J. and Jericho, K. W. F. (1986) Can. J. Vet. Res. 50:27-31; Cho et al. (1984) Can. J. Comp. Med. 48:151-155.
Electron microscopy of intact P. haemolytica A-1 cells has demonstrated the presence of two types of fimbriae. Morck et al. (1987) Can. J. Vet. Res. 51:83-88. One type is rigid and easily sheared from the cell while the other is thin and flexible. The purpose of these fimbriae has not yet been determined. For some bacteria, however, fimbriae play a role in infection. See e.g. Normark et al. (1986) in Protein-carbohydrate Interactions in Biological Systems (D. Lark ed., 1986) pp. 3-12; Mooi, F. and deGraaf, F. K. (1985) Curr. Top. Microbiol. Immunol. 118:119-136.
Group A streptococci have recently been shown to possess a surface receptor that binds to host cell plasmin but not its precursor, plasminogen. Lottenberg et al. (1987) Infect. Immun. 55:1914-1928; Broeseker et al. (1988) Microbial Pathogenesis 5:19-27. Plasmin is a protease capable of hydrolyzing fibrin, extracellular matrix proteins and several plasma proteins. Therefore, it may be an important bacterial virulence mechanism and a potential immunogen.